Efficient depolymerization of biopolymers derived from renewable resources represents a great challenge for modern chemistry due to the complexity of starting materials as well as product mixtures generated. It requires specially tailored reaction conditions and catalysts capable of selective bond cleavage reactions. Aromatics are an important target compound group since they incorporate valuable structural features for a variety of industrial applications.
Conventional approaches for lignin depolymerization include pyrolysis and liquefaction techniques. However, most pyrolysis and liquefaction methods mainly result in complex mixtures rather than well-defined aromatics (Zakzeski et al., 2010, Chem. Rev. 110:3552-3599; Pandey et al., 2012, Catalysis Science & Technology, 2:869-883; Huber et al., 2006, Chem. Rev. 106:4044-4098). Recently, a number of promising systems have been developed for the more controlled depolymerization of lignin. Lercher and coworkers described base catalyzed mild depolymerization of lignin to aromatics with high yield, and have shown that the composition of the product mixture strongly depended on reaction conditions (Roberts et al., 2011, Chem. Eur. J. 17:5939-5948). Catalytic hydrogenolysis of ethanol soluble lignin using was described by Ragauskas and coworkers (Nagy et al., 2009, Holzforschung 63:513-520). Efficient hydrogenolysis of in situ and isolated lignins was reported by Torr and coworkers using palladium on carbon resulting in good yields of biooils that mainly contained aromatic monomers and dimers (Torr et al., 2011, Bioresour. Technol. 102:7608-7611). Chang described the selective production of 4-ethylphenolics via mild hydrogenolysis, albeit with moderate product yields (Ye et al., 2012, Bioresour. Technol. 118:648-651). Depolymerization and hydrodeoxygenation of switch grass lignin with formic acid was described by Jones (Xu et al., 2012, ChemSusChem 5:667-675). Lignin depolymerization using earth-abundant metal-based catalysts is also getting increasing attention (Song et al., 2013, Science 6:994-1007; Wang and Rinaldi, 2012, ChemSusChem 5:455-1466). Ni-catalyzed cleavage of aryl ethers in the aqueous phase under mild reaction conditions was recently described (He et al., 2012, J. Am. Chem. Soc. 134:20768-20775). Furthermore, cleavage and hydrodeoxygenation of linkages relevant to lignin conversion with Pd/Zn synergistic catalysis was studied by Abu-Omar and coworkers (Parsell et al., 2013, Chem. Sci. 4:806).
Ford and coworkers have described quantitative depolymerization of organosols lignin (Barta et al., 2010, Green Chemistry 12:1640-1647; U.S. patent application Ser. No. 12/885,397) as well as cellulose and raw lignocelluloses (Matson et al., 2011, J. Am. Chem. Soc. 133:14090-14097; U.S. patent application Ser. No. 12/885,397) over a hydrotalcite derived copper-doped porous metal oxide catalyst (Cu20PMO). That process takes place in supercritical methanol and the hydrogen equivalents needed for depolymerization and further reductions originate from the solvent itself upon its reforming. Those studies targeted liquid fuels as products therefore extensive reduction/deoxygenation was desired. Indeed, the aromatic intermediates formed via hydrogenolysis when organosols lignin was used as substrate rapidly underwent further reduction to cyclohexanol derivatives (Barta et al., 2010, Green Chemistry 12:1640-1647).
Interest in corn stover as a feedstock has led to extensive research and investment into the conversion of cellulose and hemicellulose to ethanol by U.S agencies such as DOE, EPA, and DOD, and national FFDRCs such as the National Renewable Energy Laboratory (NREL), as well as by private companies such as Dupont, DSM, Archer Daniels Midland, and Mascoma. As a result, corn stover fermentation plants are being built, and these plants will be generating large amounts of corn lignin as byproduct. Lignin is the second largest component of corn stover after carbohydrates and represents about 18% of the overall mass. Currently, the corn lignin is viewed as a low-value byproduct that is burned on-site for its fuel value. Finding a higher-value chemical use for this material would dramatically improve the economics of the corn stover biorefinery and would further provide a new source of aromatic building blocks, such as phloretic acid, for the chemical industry.
Phloretic acid methyl ester has also been modified through reduction to make diols, such as 4-hydroxybenzenepropanol (Tetrahedron Letters 48 (2007) 8540-8543; U.S. Pat. No. 7,314,889). 4-hydroxybenzenepropanol has found use in polymers (Chemical & Pharmaceutical Bulletin (2001), 49(9), 1234-1235; Polymer (2011), 52(10), 2157-2162.), pharmaceuticals (PCT Int. Appl. (1999), WO 9962878 A1 19991209), and other applications such as photoactive agents (Polymers for Advanced Technologies (2013), 24(5), 473-477; Macromolecules (2001), 34(13), 4291-4293).
Phloretic acid is a naturally occurring molecule that has been extensively studied and has long been viewed as a potentially valuable molecule for a variety of applications. The synthesis of phloretic acid has been presented from variety of chemical precursors. In one example, phenol was alkylated with acrylonitrile in the presence of AlCl3 at 80-120° C. (Chinese Patent Application No. 1200367). Phloretic acid may be synthesized as one example of w-arylalkanoic acids through a Willgerodt-Kindler reaction employing a catalyst comprising HOAc, Ac2O, H2SO4, H2S, AcNMe2, DMF, or Na2SO4 (U.S. Pat. No. 5,149,866). De-tert-butylation of 3-(3,5-ditertiary butyl-4-hydroxyphenyl)propionic acid may also yield phloretic acid (Japanese Patent Application No. 63227542). Other examples include alkylation of phenol with acrylonitrile (U.S. Pat. No. 2,789,995) or electrochemical synthesis in the presence of CO2 (French Patent Publication No. 2609474). Apart from the chemical synthesis, phloretic acid has been reported as a compound of a naturally obtained mixture, olive pulp biomass with high phenolic antioxidant content described (European Patent Application No. 1844666).
Phloretic acid has been reported for use in variety of applications, particularly as a precursor for pharmaceuticals or cosmetics, such as in the preparation of antitumor agent 3(4,6)-hydroxy-2-acylphenylacetate (Chinese Patent Publication No. 101407459) or in the synthesis of immunosuppressant and antiproliferative agents (PCT Patent Publication No. 2001072733). Additionally, antihypertensives and ACE inhibitors containing phenylcarboxylic acids, 5-phenyl-γ-valerolactones, or 5-phenyl-4-hydroxyvaleric acids can be synthesized from phloretic acid (Japanese Patent No. 2012144532). p-hydroxycinnamic acid derivatives have also been used in cosmetic or dermatological compositions are discussed (U.K. Patent No. 2431876). Phloretic acid can also be a component of a deodorant (German Patent Application No. 102007028508) and of a skin care cream (Chinese Patent Publication No. 1785158).
Applications of phloretic acid have also been reported in the field of polymers and lubricants, such as the possibility of polymerizing derivatives of phloretic acid (U.K. Patent Application No. 1225290). Feijen and coworkers described injectable chitosan-based hydrogels with phloretic acid as a main ingredient that could serve as artificial extracellular matrix for cartilage tissue engineering (Feijen et al., 2004, Polymer, 45:4653-4662). Other applications include a biodegradable aliphatic/aromatic copolyester polymer from phloretic acid (Korean Patent Publication No. 20060094419), liquid-crystalline hyperbranched and potentially biodegradable polyesters based on phloretic acid and gallic acid (Kricheldorf et al., 1999, Macromolecular Chemical Physics, 200:1784-1791), and uses of lubricating oil antioxidants and stabilizers in the form of (ω-4-hydroxyphenyl)carboxylates (PCT Patent Publication No. 2004050671).
Phloretic acid has been identified as a component of different systems. Examples include phloretic acid as a component of a solder-resistant epoxy resin (Japanese Patent Publication No. 2011046866), a plant growth promoter (Japanese Patent No. 2011162454), and low caloric fat replacers (EP2332427). Phloretic acid has also been described in the preparation of such materials as a compound reducing bitterness of flavan-3-ol (WO2010026003), cyhalothrin derivatives (CN102417468) and optically active IR-absorbing polyurethane (CN101967220).
Phloretic acid has also been identified as a component of several natural compounds. Bartsch and coworkers isolated and purified major phenolic antioxidants, including phloretic acid, from two types of brined olives (Bartsch, et al., 2003, Food and Chemical Toxicology 41:703-717). Ralph and Lu identified the presence of p-coumaroylated units in lignins (Ralph and Lu, 1999, Journal of Agricultural and Food Chemistry, 47:1988-1992), while Yamagata and Sakata determined that phloretic acid is a component of raw dent corn (Sakata and Yamagata, 1980, Journal of the Agricultural Chemical Society of Japan, 54:959-964).
There is a need in the art for energy-efficient methods of depolymerizing lignin from corn stover in order to produce simple mixtures of aromatic products, such as phloretic acid and its derivatives. The present invention addresses this unmet need.